One of the major obstacles of cancer chemotherapy is lack of tumor specificity which leads to life-threatening toxicity. Tumor selectivity can be enhanced by creating relatively non-toxic prodrugs that are selectively activated in the tumor microenvironment by enzymes, which liberate the anti-neoplastic agent from the prodrug. Tumor cells secrete factors that promote an inflammatory microenvironment enriched in activated myeloid cells, which play a crucial role in facilitating tumor progression, metastasis and angiogenesis. Tumor-infiltrating macrophages and neutrophils secrete factors such as matrix metalloproteinases that enhance tumor growth and invasiveness. Treatment of solid tumors with prodrugs that are selectively activated by enzymes secreted by macrophages or neutrophils is a promising method to enhance the therapeutic index of treatment.
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